The development of head and neck cancer may depend upon an interaction both environmental carcinogens and a genetic susceptibility to those carcinogens. The need to understand such interaction in the head and neck cancer population is heightened by their associated risk for the development of second primary neoplasias, such as lung and digestive tract cancers. With an improved understanding, the relative risk of second malignancies can be more precisely defined. Preventive therapy could then be more appropriately targeted. The head and neck cancer population thus represents a potential target population for prevention of multiple diverse environmentally-induced cancers. It will, therefore be demonstrated by this proposal, that head and neck cancer patients express chromosomal susceptibility to mutagens. Specifically, cultured lymphocytes will be exposed to the clastogen bleomycin, arrested in metaphase, and assessed for bleomycin-induced chromatid breaks in cytogenetic preparations. Results gathered from the head and neck cancer population will be compared to age- and sex-matched non-cancer afflicted controls. Using case-control epidemiologic methodology, chromosome sensitivity will be evaluated as a risk factor for head and neck cancer development. Finally, the relationship of total carcinogen exposure (namely, to tobacco and alcohol) both before and after treatment to probability of second malignancy development will be identified through the formulation of a quantitative risk assessment model. The impact of adding quantitative measures of a respective patient's mutagen-hypersensitivity, as determined by the bleomycin assay, to the quantitative risk assessment model will be demonstrated. Results from this study will form a basis for determining the potential biologic significance of chromosomal sensitivity in cancer development. Results will, likewise provide insight into future stratification considerations for therapeutic intervention trials involving prevention of second malignancies in the head and neck cancer population.